Relieving the Pain

July 13, 2011

“As an internist, pain is the most common physical symptom I see,” says Erin Krebs, M.D. “But, honestly, in training, I didn’t get a lot of education about how to handle it, what to do about it, how to diagnose it. And that really bothered me.”

Krebs is a Department of Veterans Affairs (VA) Fellow in the Robert Wood Johnson Foundation (RWJF) Physician Faculty Scholars program (2009 – 2012) and an alumna of the RWJF Clinical Scholars program. She says her experience in the two programs has helped give her the tools to help fill the research gap about treating pain.

Her most recent study focuses on the safety of two related medications commonly prescribed for pain, long-acting morphine and methadone. The conclusion: Methadone was not associated with excess deaths compared with morphine among patients under the care of a physician—a finding that supports its continued use as one option for chronic pain management.

Methadone has developed a bad reputation, Krebs says, because it is more frequently implicated in overdose deaths than is morphine. She notes that studies of coroners’ reports have found that “methadone seems to be responsible for a disproportionate share of opioid-related deaths.” One big problem with those studies from the perspective of a physician, Krebs explains, is that while the population studied in coroners’ reports may all have died with opioids in their system, the drugs may not have been prescribed for them. Krebs wanted to focus on the clinical use of the pain medications—in settings in which the two drugs are prescribed and taken under the supervision of a physician.

Her study, conducted with RWJF Clinical Scholars program alumna Judy Zerzan, M.D., M.P.H., and a number of other colleagues from major universities and medical centers, was published in the April edition of the journal PAIN. It examines the experiences of more than 100,000 patients treated at VA facilities between 2000 and 2007. Krebs is a VA primary care doctor and scientist at the Roudebush VA Medical Center in Indianapolis, as well as an assistant professor of medicine at Indiana University.

The first challenge for Krebs and her colleagues was to figure out what distinguished the patients who got methadone from those who got morphine, so that whatever factors prompted physicians to prescribe one drug instead of the other could be accounted for. The researchers identified a number of differences, including patients’ ages and whether they had multiple conditions, psychiatric problems or substance use disorders.

Another factor that required analysis was where patients were treated, which she surmised could be a reflection of prescription trends in particular VA hospitals driven by the preferences of influential physicians or by some other factor.

The researchers then sorted their results to account for those factors, looking for differences in mortality rates and determining whether any such differences were attributable to the drugs prescribed. Although they cautioned that other, unmeasured, factors could still bias results, researchers concluded that patient mortality rates were lower for methadone than for morphine, and significantly lower in most cases.

The Clinical Implications

The finding could have a very real impact on how patients with pain are cared for. Doctors choose which pain medications to prescribe for a variety of reasons, but one important characteristic of methadone is its price. In Krebs’ words, “It’s dirt cheap.”

That doesn’t mean it should be dispensed casually, Krebs hastens to add. She notes that if they take it incorrectly, it might be easier for patients to overdose on methadone than on morphine. In addition, she explains, methadone has been found to have an effect on the heart’s electrical patterns, which could lead in rare cases to sudden death. For these and other reasons, the Food & Drug Administration issued an alert in 2006, cautioning physicians to take care in prescribing it.

Nevertheless, while Krebs and her colleagues believe more research is needed, their findings indicate that methadone is not responsible for excess deaths among patients taking it under the supervision of a physician.